Binding-induced folding of a natively unstructured transcription factor.

ABSTRACT: Transcription factors are central components of the intracellular regulatory networks that control gene expression. An increasingly recognized phenomenon among human transcription factors is the formation of structure upon target binding. Here, we study the folding and binding of the pKID domain of CREB to the KIX domain of the co-activator CBP. Our simulations of a topology-based Gō-type model predict a coupled folding and binding mechanism, and the existence of partially bound intermediates. From transition-path and Phi-value analyses, we find that the binding transition state resembles the unstructured state in solution, implying that CREB becomes structured only after committing to binding. A change of structure following binding is reminiscent of an induced-fit mechanism and contrasts

SUBMITTER: Turjanski AG 

PROVIDER: S-EPMC2289845 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature